Rituximab to Treat Neuropathy With Anti-MAG Antibodies
This study will test the safety and effectiveness of the drug Rituximab in treating a nerve disease called MGUS (also known as neuropathy with anti-MAG antibodies). Patients with MGUS have an abnormal protein called monoclonal IgM immunoglobulin that attacks the myelin sheath (protective coating) of nerves, causing them to not function properly. The disease affects the nerves in the legs or arms, and patients have numbness, tingling, muscle weakness, and unsteady gait. There are no adequate treatments. Immunosuppressive drugs or human immunoglobulin infusions can produce mild and transient improvement, but the benefits of these therapies are not significant.
The abnormal immunoglobulin protein in MGUS is produced by white cells called B lymphocytes. Rituximab is approved to treat B cell lymphomas. Also, the drug showed promise in a recent study of patients with demyelinating neuropathy associated with production of antibodies from B lymphocytes directed against certain nerve proteins. Although the number of patients treated with Rituximab was small, the drug was well tolerated and caused significant improvement in several of the patients.
Patients 25 years of age and older with MGUS may be eligible for this 2-year study. Candidates will be screened with a medical history, physical and neurological examinations, and blood tests.
Participants will be randomly assigned to receive intravenous (through a vein) infusions of either Rituximab or placebo (a solution that looks like Rituximab but has no active ingredient) once a week for 4 consecutive weeks. In addition, they will undergo the following tests and procedures:
- Monthly follow-up visits following Rituximab treatment for repeat physical and neurological examinations, blood tests, muscle strength measurements, and review of signs and symptoms.
- Two sessions of lymphapheresis, one at the beginning of the study and one a year later-to collect lymphocytes. For this procedure, whole blood is drawn through a needle in an arm vein, much like donating a unit of blood. The blood then flows through a catheter (plastic tube) into a cell separating machine, where the white blood cells are extracted and removed. The red cells and plasma are then returned to the body through a needle in the other arm. The procedure takes about 60 to 90 minutes.
- Electrophysiologic studies (electromyography and nerve conduction testing) are done once at the beginning of the study and again one year later. For electromyography, a small needle is inserted into a few muscles and the patient is asked to relax or to contract the muscles. The electrical activity of the muscle cells is recorded and analyzed by a computer. For nerve conduction testing, nerves are stimulated through small wire electrodes attached to the skin and the response is recorded and analyzed.
If this study indicates that Rituximab is beneficial against MGUS, patients who were assigned to receive placebo during the trial will be offered treatment with Rituximab (four weekly infusions) at the end of the study.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Safety, Tolerability, and Efficacy of Rituximab in Patients With Anti-Glycoconjugate Antibody-Mediated Demyelinating Neuropathy: A Double-Blind Placebo-Controlled Randomized Trial|
- Changes in neurological performance using the INCAT scales. [ Designated as safety issue: No ]
|Study Start Date:||November 2002|
|Estimated Study Completion Date:||October 2007|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00050245
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|